ArticleInternational journal of molecular sciences2026
Integrating Mutation-Derived and Expression Features from Single-Cell RNA Sequencing: Pitfalls of Standard Cross-Validation in Small-Cohort Settings.
Article in International journal of molecular sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Single-cell RNA sequencing (scRNA-seq) studies increasingly combine expression-based and mutation-derived signals, but small-cohort designs with repeated runs from the same biological unit can make standard cross-validation overly optimistic. We reanalyzed PRJNA736095 (14 SRR runs from 7 GSM/donor proxies) using a GATK-centered RNA-seq variant-calling and gene-burden workflow, then evaluated mutation-derived, expression-only, and combined feature sets with leakage-safe preprocessing inside each validation fold. Run-level repeated stratified cross-validation showed high within-dataset separability for GATK gene-burden features (balanced accuracy 0.973 +/- 0.113), but GSM-grouped leave-one-GSM-out validation reduced balanced accuracy to 0.708 and exact GSM-level permutation testing was not significant (
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